Donepezil treatment of patients with severe Alzheimer's disease in a Japanese population: Results from a 24-week, double-blind, placebo-controlled, Randomized trial

Background/ Aims: A 24- week, randomized, parallel-group, double-blind placebo-controlled study was conducted to evaluate the efficacy and tolerability of donepezil in severe Alzheimer's disease ( AD). Methods: Patients with severe AD (Mini- Mental State Examination score 1-12; modified Hachinski Ischemic Score <= 6; Functional Assessment Staging 6 6) were enrolled in this study in Japan. A total of 325 patients were randomized to donepezil 5 mg/day (n=110), donepezil 10 mg/ day ( n= 103) or placebo (n= 112). Primary outcome measures were change from baseline to endpoint in the Severe Impairment Battery ( SIB) and Clinician's InterviewBased Impression of Change-plus caregiver input (CIBICplus) at the endpoint visit. Results: Donepezil 5 mg/ day and 10 mg/ day were significantly superior to placebo on the SIB, with a least-squares mean treatment difference of 6.7 and 9.0, respectively (p < 0.001 compared with placebo). CIBIC-plus analyses showed significant differences in favor of donepezil 10 mg/day over placebo at endpoint ( p = 0.003). A statistically significant dose-response relationship was demonstrated with the SIB and CIBIC- plus. Donepezil was well tolerated. Conclusion: This study confirmed the effectiveness of donepezil 10 mg/ day in patients with severe AD and demonstrated a significant dose-response relationship. Donepezil at dosages of both 5 mg/ day and 10 mg/ day is safe and well tolerated in Japanese patients with severe AD. Copyright (c) 2008 S. Karger AG, Basel.